Linked Life Data

19136579

Source:http://linkedlifedata.com/resource/pubmed/id/19136579

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-27
pubmed:abstractText
We recently provided evidence that anti-inflammatory macrophage activation, i.e., the inhibition of constitutive and signal-induced NF-kappaB activity by the pulmonary collectin surfactant protein (SP)-A, critically involves a promoted stabilization of IkappaB-alpha, the predominant inhibitor of NF-kappaB, via posttranscriptional mechanisms comprising the activation of atypical (a)PKCzeta. SP-A uptake and degradation by alveolar macrophages (AMphi) occur in a receptor-mediated, clathrin-dependent manner. However, a mutual link between endocytosis of and signaling by SP-A remains elusive. The aim of this study was to investigate whether clathrin-mediated endocytosis (CME) of SP-A by AMphi is a prerequisite for its modulation of the IkappaB-alpha/NF-kappaB pathway. The inhibition of clathrin-coated pit (CCP) formation and clathrin-coated vesicle (CCV) formation/budding abrogates SP-A-mediated IkappaB-alpha stabilization and SP-A-mediated inhibition of LPS-induced NF-kappaB activation in freshly isolated rat AMphi, as determined by Western analysis, fluorescence-activated cell sorting, confocal microscopy, and EMSA. Actin depolymerization and inhibition of CCP formation further abolished SP-A-mediated inhibition of LPS-induced TNF-alpha release, as determined by ELISA. In addition, SP-A-induced atypical PKCzeta activation was abolished by pretreatment of AMphi with CCV inhibitors as determined by in vitro immunocomplex kinase assay. Although CME is classically considered as a means to terminate signaling, our results demonstrate that SP-A uptake via CME by AMphi has to precede the initiation of SP-A signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L430-41
pubmed:meshHeading
pubmed-meshheading:19136579-Actins, pubmed-meshheading:19136579-Animals, pubmed-meshheading:19136579-Base Sequence, pubmed-meshheading:19136579-Clathrin, pubmed-meshheading:19136579-Clathrin-Coated Vesicles, pubmed-meshheading:19136579-DNA, pubmed-meshheading:19136579-Endocytosis, pubmed-meshheading:19136579-I-kappa B Proteins, pubmed-meshheading:19136579-Lipopolysaccharides, pubmed-meshheading:19136579-Macrophage Activation, pubmed-meshheading:19136579-Macrophages, Alveolar, pubmed-meshheading:19136579-Male, pubmed-meshheading:19136579-Molecular Chaperones, pubmed-meshheading:19136579-NF-kappa B, pubmed-meshheading:19136579-Pulmonary Surfactant-Associated Protein A, pubmed-meshheading:19136579-Rats, pubmed-meshheading:19136579-Rats, Sprague-Dawley, pubmed-meshheading:19136579-Signal Transduction, pubmed-meshheading:19136579-Tumor Necrosis Factor-alpha
pubmed:year
2009
pubmed:articleTitle
Role of clathrin-mediated endocytosis of surfactant protein A by alveolar macrophages in intracellular signaling.
pubmed:affiliation
Department of Clinical Medicine, Division of Cellular Pneumology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't